Neoadjuvant Chemoimmunotherapy in Recurrent Glioblastoma

Sponsor
University of Louisville (Other)
Overall Status
Recruiting
CT.gov ID
NCT05700955
Collaborator
(none)
30
1
2
26
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Study Details

Study Description

Brief Summary

The primary purpose of this study is to test the safety of Pembrolizumab and Temozolomide in treating recurrent glioblastoma and to characterize the effect of this treatment on the participants tumor and immune system..

Condition or Disease Intervention/Treatment Phase
  • Drug: Pembrolizumab and Temozolomide
Phase 1

Detailed Description

Participants will undergo screening tests to determine if they are eligible to participate. This will involve a complete history and physical examination, vital signs, blood tests including complete blood count (CBC), and serum chemistry (CMP).

Participants will receive one cycle of Temozolomide and Pembrolizumab prior to removing recurrent tumor, followed by three weekly cycles of treatment until progression.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
30 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Intervention Model Description:
The experience with neoadjuvant immunotherapy has raised the possibility of utilizing surgical resection/immunotherapy as a combination treatment for patients with recurrent glioblastoma. There are several reasons that suggest that surgical resection will likely enhance the activity of immunotherapy in glioblastoma.This includes 1) direct impact on tumor cells; 2) impact on immune cells; and 3) impact on immune infiltration. The combination of the evidence that neoadjuvant Pembrolizumab has a positive effect on GBM survival, the evidence in lung cancer that chemotherapy and checkpoint inhibitor therapies are synergistic and the clinical utility of surgery in patients with recurrent glioblastoma has suggested that the neoadjuvant administration of Pembrolizumab and temozolomide prior to and following maximal surgical resection represents a very attractive experimental combination for the treatment of recurrent glioblastoma.The experience with neoadjuvant immunotherapy has raised the possibility of utilizing surgical resection/immunotherapy as a combination treatment for patients with recurrent glioblastoma. There are several reasons that suggest that surgical resection will likely enhance the activity of immunotherapy in glioblastoma.This includes 1) direct impact on tumor cells; 2) impact on immune cells; and 3) impact on immune infiltration. The combination of the evidence that neoadjuvant Pembrolizumab has a positive effect on GBM survival, the evidence in lung cancer that chemotherapy and checkpoint inhibitor therapies are synergistic and the clinical utility of surgery in patients with recurrent glioblastoma has suggested that the neoadjuvant administration of Pembrolizumab and temozolomide prior to and following maximal surgical resection represents a very attractive experimental combination for the treatment of recurrent glioblastoma.
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I Trial of Neoadjuvant Chemoimmunotherapy in Recurrent Glioblastoma
Actual Study Start Date :
Nov 1, 2022
Anticipated Primary Completion Date :
Jan 1, 2025
Anticipated Study Completion Date :
Jan 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: temozolomide

Participants will take Temozolomide pills at home at a dose determined by body weight. They will take the pills for five days every 3 weeks. It will be dispensed by the pharmacy and must be stored in a closed container at room temperature, away from heat, moisture, and direct light and kept from freezing. It will be kept out of the reach of children. Outdated medicine or medicine no longer needed will be returned to the Brown Cancer Center pharmacy for disposal.

Drug: Pembrolizumab and Temozolomide
Characterize the safety and immunologic/genomic/metabolomic effects of neoadjuvant Pembrolizumab and Temozolomide in recurrent glioblastoma.
Other Names:
  • Pembro and Temodar
  • Experimental: Pembrolizumab

    Pembrolizumab will be administered at a dose of 200 mg as an IV infusion through a freely flowing IV. The diluted solution will be administered intravenously over 30 minutes through an intravenous line containing a sterile, non-pyrogenic, low-protein binding 0.2 micron to 5 micron in-line or add-on filter. Other drugs will not be co-administered through the same infusion line. Pembrolizumab doses will be repeated every three weeks.

    Drug: Pembrolizumab and Temozolomide
    Characterize the safety and immunologic/genomic/metabolomic effects of neoadjuvant Pembrolizumab and Temozolomide in recurrent glioblastoma.
    Other Names:
  • Pembro and Temodar
  • Outcome Measures

    Primary Outcome Measures

    1. Treatment toxicity [Change in frequency of adverse events prior to gross total resection or recurrent glioblastoma]

      Quantification of the frequency of adverse events in patients treated with neoadjuvant Pembrolizumab and Temozolomide with gross total resection of recurrent glioblastoma.

    Secondary Outcome Measures

    1. Overall Survival [Every 8 weeks for 24 months]

      Progression and response to treatment will be determined using the Response Assessment in Neuro-Oncology (RANO) criteria.

    2. Neurologic function and quality of life [Every 8 weeks for 24 months]

      Using the Neurologic Assessment in Neuro-oncology (NANO) scale on each visit. In addition, the Eastern Cooperative Oncology Group (ECOG) performance status will be monitored.

    3. Treatment Toxicity [Change in frequency of adverse events after gross total resection or recurrent glioblastoma]

      Quantification of the frequency of adverse events in patients treated with neoadjuvant Pembrolizumab and Temozolomide after gross total resection of recurrent glioblastoma.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:

    -Inclusion Criteria Patients are eligible to be included in the only if they meet all of the following criteria

    1. Histopathologically proven diagnosis of glioblastoma prior to registration, by pathology report;

    2. The tumor must be confined to the supratentorial compartment

    3. The tumor tissue block from the primary diagnosis must be available to be sent for pathology review, after registration.

    4. History/physical examination within 7 days prior to registration

    5. Karnofsky performance status ≥ 60 within 7 days prior to registration.

    6. Adequate Organ Function Laboratory Values

    • Absolute neutrophil count (ANC) ≥1,500/mcL

    • Platelets ≥100,000/mcL

    • Hemoglobin ≥9.0 g/gL or ≥5.6 mmol/L, without recent transfusion

    • Creatine ≤1.7 x upper limit of normal (ULN) or Measure or Calculated creatinine clearance ≥ 60.0mL/min for subject with creatinine levels > 1.5 X institutional ULN (GFR can also be used in place of creatinine or CrCl)

    • Total bilirubin ≤ 1.5 x ULN or Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 x ULN

    • AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN or ≤ 5 x ULN for subjects with liver metastases

    1. The patient must have completed chemoradiation with Radiotherapy and Temozolomide of the primary tumor according to standard of care.

    2. Patients must have received no more than 3 prior therapies for Recurrent High Grade Glioma.

    3. Subjects must have the ability to understand and willingness to sign a written informed consent document.

    4. Female subjects of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

    5. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication.

    6. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

    Exclusion Criteria:

    -Exclusion Criteria Patients will be excluded from the study if they meet any of the following criteria

    1. Previous use of an immunotherapy such as a vaccine therapy, dendritic cell vaccine or intracavitary or convectional enhanced delivery of therapy.

    2. Prior invasive malignancy (except non-melanomatous skin cancer) within the previous three years

    3. Severe, active co-morbidity defined as follows:

    • Transmural myocardial infarction or unstable angina within the last 6 months prior to registration

    • History of stroke, cerebral vascular accident (CVA) or transient ischemic attack within 6 months prior to registration

    • Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or clinically significant peripheral vascular disease

    • Known history of Tuberculosis or acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration

    • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration

    • Patients with active autoimmune disease or history of autoimmune disease that might recur, will be considered on an individual basis

    • Any other major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy.

    • Is pregnant or breastfeeding

    • Has received prior therapy with an anti-Programmed Death 1 (PD-1), anti- Programmed Death-ligand 1 (PD-L1), or anti- Programmed Death-ligand 1 (PD-L2) agent.

    1. Patient must have < 1.5 cm midline shift pre-operative

    2. History of severe hypersensitivity reaction to any monoclonal antibody including pembrolizumab.

    3. Patients who cannot safely undergo MRI due to non-MRI compatible pacemaker, or other reason.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 James Graham Brown Cancer Ctr. Louisville Kentucky United States 40202

    Sponsors and Collaborators

    • University of Louisville

    Investigators

    • Principal Investigator: Donald Miller, MD, University of Louisville/James Graham Brown Cancer Ctr.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Donald Miller, Donald M. Miller, M.D., Ph.D., University of Louisville
    ClinicalTrials.gov Identifier:
    NCT05700955
    Other Study ID Numbers:
    • 22.0676
    First Posted:
    Jan 26, 2023
    Last Update Posted:
    Jan 26, 2023
    Last Verified:
    Jan 1, 2023
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jan 26, 2023